tbuckley/cabot-search huggingface dataset:
Characteristics of cytokine profile of wound fluid in breast cancer patients after mammoplasty with textured implants.
Authors: Viktoria Yu Przhedetskaya, Aleksandr B. Sagakyants, Yuriy V. Przhedetskiy, Elena Yu Zlatnik, Oksana G. Shulgina, Ekaterina I. Zolotareva, Elena P. Ulianova, Elena S. Bondarenko, Viktoria V. Pozdnyakova, Yulia V. Ulianova, Viktoriya L. Volkova, Mamuka V. Bauzhadze, Irina V. Pustovaya, Natalia A. Chertova, Elena G. Goncharova, Mary L. Maldonado, Liubov Yu Vladimirova
Journal: Journal of Clinical Oncology (2022)

e12589 Background: Breast reconstruction after mastectomy for breast cancer (BC) is an important rehabilitation stage. Breast prosthesis implantation is sometimes accompanied by different complications which can be influenced by the immune system status. The aim of this study was to identify characteristics of the local cytokine profile in patients with breast cancer in the early postoperative period after reconstructive surgery with textured implants (TI). Methods: The study included 30 patients aged 32-68 years, mean age 42.9±1.98 years, with stage I-IIb BC (monocentric nodular BC, T1N0M0 - T2N1M0). All patients underwent skin-sparing mastectomy with level II axillary lymph node dissection and immediate implant reconstruction in 2017-2019. Levels of cytokines IL-1β, IL-2, IL-4, IL-6, IL-8, IFN-γ, and TNF-α were determined by ELISA in wound fluid from the cavity with TI on days 1, 3-4 and 7 after the surgery. Results: Levels of IL-6 in wound fluid of patients with TI statistically significantly decreased by 43% (p=0.036) and 41% (p=0.039) on days 3-4 and 7 after the surgery, and IL-2 decreased by 27% (p=0.045) with its further increase by 44% (p=0.037) compared to day 1. A pronounced increase of the IFN-γ levels by 118% (p=0.018) and 158% (p=0.012) was registered respectively on days 3-4 and 7 after surgery. Conclusions: Reconstructive surgery with TI is followed by a local increase in levels of IL-2 and IFN-γ which may indicate increasing antitumor potential of the microenvironment. The revealed decrease in IL-6 levels after TI implantation indicates certain features of the inflammatory reaction development in the intervention site.
MEDB-44. Transcriptomic resolution of subgroup-specific medulloblastoma architecture
Authors: Nicholas Willard, Kent Riemondy, Andrea Griesinger, Michael Kaufman, Sujatha Venkataraman, Nicholas Foreman, Rajeev Vibhakar, Andrew Donson
Journal: Neuro-Oncology (2022)

Abstract Despite a growing understanding and stratification of medulloblastoma, it remains an aggressive childhood brain tumor with high morbidity and mortality. Multimodal genomic and epigenomic analysis has permitted the classification of medulloblastoma into four subgroups with varying biology and clinical behavior: WNT, Sonic-Hedgehog (SHH), Group 3, and Group 4. In our previously published work, Single-cell RNA sequencing (scRNAseq) identified distinct tumor cell subpopulations in specific medulloblastoma groups. However, this technology is limited by its lack of architectural information. Spatial transcriptomics is a relatively new technology that permits the analysis of gene expression as it occurs within organized tissue. In our ongoing study, we utilized Visium spatial transcriptomics, integrated with scRNAseq data and immunohistochemistry, to analyze frozen samples of medulloblastomas (SHH, Group 4, and Group 3 with and without MYC amplification). In SHH in particular, we were able to identify scRNAseq populations within the geographically constricted Visium data, including SHH-C2, a population located in histologic nodules, the predominant neuronal-differentiated population SHH-C1, and progenitor populations (SHH-B1 and B2). In addition, we were able to visualize clusters not detectable by scRNAseq – a cluster lining nodules with expression of vascular endothelium marker, reticulin and M2-macrophage genes, and a novel DNA-repair cluster. In addition, Visium data permits the spatial constraint of proliferating cells, which is frequently problematic in scRNAseq, as dividing cells cluster independently. The proliferation is highest in the SHH-B2 minor progenitor population, absent in the SHH-C1 major differentiated population, and is moderate in other population including the SHH-C2 nodules. Group 3 and 4 medulloblastoma are more complex but show preliminary corroboration with scRNAseq data. In summary, Visium allows us to map subpopulations identified by scRNAseq to tumor architecture more definitively and rapidly than IHC. These novel insights advance our understanding of medulloblastoma, a critical step in improving treatment options for children with this disease.
The prognostic significance of disseminated tumor cells in bone marrow in patients with operable breast cancer: An updated analysis.
Authors: Luc Yves Dirix, Laura Van Mileghem, Annemie Prove, Peter B. Vermeulen
Journal: Journal of Clinical Oncology (2022)

e13013 Background: The main cause of death in breast cancer patients is the consequence of the spread and outgrowth of tumor cells at distant sites. The presence of disseminated tumor cells (DTCs) in the bone marrow at diagnosis is considered a predictor for metastasis. Methods: This is an updated analysis of a study in 102 patients with operable breast cancer on the significance of bone marrow micrometastases. The mean follow-up time is 127 months (range 10 - 142, median 129 months). Bone marrow aspirates were analysed for the presence of DTCs by a real time-polymerase chain reaction (RT-PCR) for cytokeratin 19 (CK) and mammaglobin (MAM).The aim of this study is to confirm the association between DTCs and disease-specific survival (DSS) as well as metastasis-free survival (MFS). Results: CK positivity was borderline significant for DSS (p = 0.054). MAM positivity was significantly prognostic for DSS with a hazard ratio (HR) of 3,110 (1,416-6,832) (p = 0,005). Patients positive for both CK and MAM did have a significant worse outcome with a HR for DSS of 7,329 (2,361 – 22,752) (p = 0,001). No significant influence on MFS was identified for CK (p = 0,658) or MAM positivity (p = 0,095). The combination of CK and MAM positivity did however confer a significantly increased risk for MFS (p = 0,043) at a HR of 4,126 (1,409-12,082). Conclusions: This study confirms the role of DTCs as a negative, prognostic factor in patients with operable breast cancer. The combination of CK and MAM is useful to identify this increased risk.
Correlating electrical dysfunctions and structural remodeling in Arrhythmogenic Mouse Hearts by advanced optical methods
Authors: F Giardini, C Olianti, V Biasci, G Arecchi, T Zaglia, M Mongillo, E Cerbai, C Zgierski-Johnston, P Kohl, L Sacconi
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union’s Horizon 2020 research and innovation programme - No 952166 (REPAIR) Regione Toscana - Bando Ricerca Salute 2018 - PERCARE project. Severe remodeling processes may occur in the heart due to both genetic and non-genetic diseases. Structural remodeling, such as collagen deposition (fibrosis) and cellular misalignment, can affect electrical conduction at different orders of magnitude and, eventually, lead to arrhythmias. In this scenario, arrhythmogenic cardiomyopathy (ACM) is an inherited heart disease that involves ventricular dysfunction, arrhythmias, and localized replacement of contractile fibers with fibrofatty scar tissue. Unfortunately, nowadays, predicting the impact of fine structural alterations on the electrical dysfunction in entire organs is challenging, due to the inefficacy of standard imaging methods in performing high-resolution three-dimensional reconstructions in massive tissues. In this work, we developed a new full-optical correlative approach to quantify and integrate the electrical dysfunctions with three-dimensional structural reconstructions of entire hearts, both in controls and in a mouse model of ACM. We combined optical mapping of the action potential propagation (APP) with advances in tissue clearing and light-sheet microscopy techniques. First, we employed an optical platform to map and analyze the APP in Langendorff-perfused hearts. Then, we optimized the SHIELD procedure for the clearing of cardiac tissue, thus converting the previously electrically characterized samples into well-preserved and fully-transparent specimens. A high-throughput light-sheet microscope has been developed following the mesoSPIM project: the conceived microscope allows the reconstruction of the whole mouse heart with a micrometric resolution allowing fine quantification of myocytes alignment and fibrosis deposition across the organ. Finally, we developed a software pipeline that employs high-resolution 3D images to analyze and co-register APP maps with the 3D anatomy, contractile fibers disarray, and fibrosis deposition on each heart. We believe that this promising methodological framework will allow clarifying the involvement of fine structural alterations in the electrical dysfunctions, thus enabling a unified investigation of the structural causes that lead to electrical and mechanical alterations after the tissue remodeling.
Applying Lean Kaizen to improve timely CT scan appointments for oncology patients in a safety-net hospital.
Authors: Brian Ho, Raisa Epistola, Sally Leong, Sana Ali, Rachel Germono, Denise Ranada, Christopher Kummerfeldt, Vrunda Patel, Annette Berbano, Annette Berbano, Minni Kannampuzha, Larissa Celles, Adriana Pena, Leslie Balderas, Sharon Ellis, Brenda Martinez Abarca, Griselda Gutierrez, John Shim, Jennifer Minkyoung Lee, James Jen-Chi Yeh
Journal: Journal of Clinical Oncology (2022)

e18627 Background: Timely radiographic studies are essential to oncology care. At our institution, a safety net hospital in a large metropolitan area, baseline assessment determined that the overwhelming majority of outpatient computed tomographic (CT) scans for oncology patients were overdue for scheduling. We applied the Lean Kaizen quality improvement model to improve on-time scheduling of CT scans in our hematology-oncology clinic. Lean Kaizen is centered around eliminating waste, improving productivity, and maintaining sustained improvement through collaborative efforts from multiple departments to analyze system workflow inefficiencies in a stepwise fashion. Methods: In collaboration with our Kaizen Promotion Office, we conducted a series of interdisciplinary meetings including staff from radiology, oncology, scheduling, and administration. All aspects of the scheduling workflow were critically reviewed and barriers to scheduling were identified using an Ishikawa root-cause diagram and the Kaizen principle of gemba (“go and see the work”). A new workflow was developed in which clinic staff scheduled patients for CT scans prior to clinic discharge. To implement the new workflow, we employed the principles of shojinka (“create flow”) and nagara (“eliminate waste”). We developed and distributed workflow guides, conducted simulation events, and provided one-on-one training to ensure a successful rollout. Three months after our initial meeting, the new workflow was launched. The workflow was refined based on feedback from daily pre-clinic team meetings. Results: Preliminary data were gathered approximately 3 weeks following implementation of our new workflow. Since our intervention, the percentage of CT scans overdue for scheduling decreased from 87% (65 of 75 CT scans) to 17% (9 of 53 CT scans). Conclusions: Our study showed that the Lean Kaizen QI model was successful in improving the rate of oncology patients scheduled for CT scans in a timely fashion. This study demonstrated the importance of interdepartmental collaboration and continuous monitoring for improvement. Given the success of this project, this workflow will be expanded to other services within our institution following the Kaizen principle of yokoten (“sharing knowledge”).
Factors influencing the initiation of adjuvant endocrine therapy in patients with Estrogen receptor-positive ductal carcinoma in situ: A single institution experience.
Authors: Fady Farag, Julia Levy, John T. Cole
Journal: Journal of Clinical Oncology (2022)

e18569 Background: Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive ductal breast cancers. The aim of treatment in DCIS is to prevent local recurrence as almost half of recurrences can be invasive. Few studies have specifically addressed how provider recommendation and patient’s demographic factors contribute to medication initiation in women with DCIS. The objective of this study is to evaluate whether disparities exist pertaining to prescription of adjuvant hormonal therapies. Methods: This single-center retrospective study included 111 patients diagnosed with DCIS between 2020 and 2021. Data collected included race, type of insurance, prescribing providers, and socioeconomic status. We used zip codes to identify the poverty levels in these areas as published in the United States Census Bureau and stratified the patients into quartiles accordingly. Chi-Square statistics were used to calculate significance levels. Results: The average age was 62.8. 63 (56.8%) patients received adjuvant hormonal therapy, and 48 (43.2%) did not. White patients comprised 53.1% of the population, while African Americans were 45%. Among the white patients, 52.5% took hormonal therapy, while 62% of African Americans received hormonal treatment. Majority had Medicare insurance (49.5%), or a commercial insurance (42.3%). 62% of Medicare patients received hormonal therapy and 52.5% of commercial insurance users received adjuvant treatment. 34% lived in areas with the percentage below poverty line greater than 21.9%, 27% lived in areas with the percentage below poverty line between 16.4-21.9%, 38.7% % lived in areas with the percentage below poverty line between 10.6% and 16.4%, and 9% lived in areas with the percentage below poverty line was less than 10.6%. Providers were grouped into either breast oncologist or general oncologists. Breast oncologists prescribed hormonal treatment to 56.8% of their patients, and general oncologists to 56.7% of their patients. There was no statistical significant correlation between the intake of hormonal therapy and race (P = 0.6), insurance (P = 0.5), socioeconomic (P = 0.58) or providers (P = 0.99). Conclusions: In this single-center study, we didn’t find that patients’ demographics or providers influenced the decision to initiate adjuvant hormonal therapy in DCIS.
Prognosis value of preoperative biomarkers: Neutrophil-to-lymphocyte Ratio, Monocyte-to-lymphocyte Radio and Platelet-to-Lymphocyte Ratio in patients undergoing radical nephroureterectomy for upper tract urothelial carcinoma
Authors: S. Zouari, A. Saadi, N. Setti Boubaker, M. Chakroun, B. Saidani, M. Ayadi, F. Ksontini, M. Ksontini, A. Blel, H. Boussaffa, A. Bouzouita, A. Derouiche, R. Ben Slama, H. Ayed, A. Mezlini, S. Rammeh, M. Chebil
Journal: European Urology (2022)
Clinical characterization and outcomes of prostate cancer patients undergoing immediate vs. conservative management: A PIONEER study
Authors: G. Gandaglia, M.I. Omar, G. Maresca, A. Golozar, S. Remmers, M.J. Roobol, C. Steinbeisser, T. Hulsen, K. Van Bochove, B. Katharina, M. Van Hemelrijck, P-P.M. Willemse, M. Oja, S. Tamm, S. Reisberg, J. Gomez Rivas, R. Van Den Bergh, A. Kinnaird, A. Asiimwe, A. Bjartell, E.J. Smith, J. N'Dow
Journal: European Urology (2022)
Perioperative and functional outcomes of off-Clamp robotic partial nephrectomy for purely hilar versus abutting the hilum and central tumors
Authors: M. Ferriero, M. Costantini, R. Mastroianni, G. Tuderti, U. Anceschi, L. Misuraca, A. Brassetti, A. Bove, S. Guaglianone, M. Gallucci, G. Simone
Journal: European Urology (2022)
Selective removal of soluble tumor necrosis factor receptors by apheresis as a novel immunotherapy approach for triple-negative breast cancer.
Authors: Adam Ostrowski, Robert Segal, Lawrence Florin, Nina Anderson, Victoria G. Manax, Annette Marleau, Steven Josephs, Piotr Jan Wysocki, Kamil Wladyslaw Konopka, Lukasz Kwinta, Pawel Michal Potocki
Journal: Journal of Clinical Oncology (2022)

e13065 Background: Although the activity of the cytokine TNF-α against diverse tumor types has been widely documented, safe and effective therapies for augmenting this pathway are lacking. An immunoadsorption device, the LW-02 Column, has been developed as a subtractive immunotherapy approach to remove soluble TNF-α receptors (sTNF-R1 and sTNF-R2) from cancer patients’ plasma using apheresis. Since soluble TNF-α receptors bind to and neutralize the activity of TNF-α, their depletion from plasma is performed to unleash the anti-tumor effects of endogenous TNF-α. The LW-02 Column contains an inert matrix to which a recombinant TNF-α polypeptide (single-chain TNF-α; scTNF) is covalently coupled as a ligand for capturing sTNF-R1 and sTNF-R2. This study evaluated key performance features of the LW-02 Column when used as a monotherapy or with chemotherapy in patients with advanced TNBC [ClinicalTrials.gov Identifier: NCT04004910]. Methods: As part of the ongoing clinical study, 28 patients with advanced TNBC underwent 862 LW-02 Column Immunopheresis procedures at 3 sites (mean=22.5; range=2–109) using the Spectra Optia Apheresis System (Terumo BCT, Inc.); 10 patients received LW-02 Column monotherapy and 18 received LW-02 Column therapy with various chemotherapy regimens. Therapy with the LW-02 Column was performed 3x/week for at least 16 weeks by processing 2 plasma volumes per treatment. Adverse events and tolerability of the therapy were monitored. Assessments were performed to determine the LW-02 Column’s target specificity and capture efficiency. The amount of scTNF ligand that could leach from the column during the procedures was also measured. Results: No serious device-related adverse events have been reported in this study. After 30 minutes of apheresis using the LW-02 Column, the mean capture efficiencies for sTNF-R1 and sTNF-R2 from TNBC patients’ plasma were 95.2% and 79.6%, respectively. The LW-02 Column was highly selective for removing sTNF-R1 and sTNR-R2 from total plasma proteins. The mean total amount of scTNF that may leach from the LW-02 Column (109 ng per apheresis session) is orders of magnitude lower than TNF-α concentrations that are known to trigger clinically meaningful effects. Conclusions: In patients with advanced TNBC, subtractive immunotherapy with the LW-02 Column either as a monotherapy or with chemotherapy is safe and achieves effective depletion of soluble TNF-α receptors from plasma. Evaluation of the safety and efficacy of the LW-02 Column is ongoing in TNBC patients as well as in studies of other solid tumor types. The LW-02 Column provides a novel and promising immunotherapy approach for augmenting the anti-cancer activity of the TNF-α pathway. Clinical trial information: NCT04004910.
Progression-free survival after second line of therapy (PFS-2) for metastatic clear cell renal cell carcinoma (ccRCC) in patients treated with first-line immunotherapy combinations.
Authors: Kelly N. Fitzgerald, Cihan Duzgol, Andrea Knezevic, Natalie Shapnik, Ritesh Kotecha, David Henry Aggen, Maria Isabel Carlo, Neil J. Shah, Martin H Voss, Darren R. Feldman, Robert J. Motzer, Chung-Han Lee
Journal: Journal of Clinical Oncology (2022)

4536 Background: Front-line therapy with immunotherapy combinations is standard of care for metastatic ccRCC, with ipilimumab/nivolumab (IO/IO) and several combinations of a VEGFR-targeted tyrosine kinase inhibitor with a PD-1 inhibitor (TKI/IO) showing superior efficacy to TKI monotherapy. PFS-2 evaluates the ability to be salvaged by 2 nd line therapy and is a surrogate for overall survival (OS). PFS-2 was compared in patients receiving 1 st line IO/IO vs TKI/IO for metastatic ccRCC. Methods: A retrospective analysis was performed on patients with ccRCC treated at Memorial Sloan Kettering Cancer Center between 1/1/2014 and 12/30/2020, in cohorts defined by 1 st line: IO/IO or TKI/IO. PFS-2 is defined as time from start of 1 st line to progression on next therapy, or death. Patients without a PFS-2 event were censored at a prespecified cutoff date. Objective response rate to 1 st (ORR 1st ) and 2 nd (ORR 2nd ) line are compared with the Fisher’s exact test. OS, PFS-2, and time on therapy are estimated with the Kaplan-Meier method and compared with the log-rank test. Results: One hundred seventy-three patients received 1 st line IO/IO (N = 90) or 1 st line TKI/IO (N = 83); respectively, 52 and 40 patients had a PFS-2 event. 1 st line TKI/IO regimens included: 34% axitinib/pembrolizumab, 29% lenvatinib/pembrolizumab, 25% axitinib/avelumab, 11% other. More IO/IO patients had brain metastases and intermediate/poor MSKCC risk category (respectively p = 0.007, p &lt; 0.001). ORR 1st and median months on 1 st line were higher with TKI/IO vs IO/IO (65% vs 39%, p &lt; 0.001; 16.1 vs 5.1, p &lt; 0.001). ORR 2nd was higher with IO/IO vs TKI/IO (47% vs 13%, p &lt; 0.001), and median months on 2 nd line was not significantly different (7.7 vs 7.1, p = 0.30). Median PFS-2 for TKI/IO was 44 months (95% CI: 27, 53) vs 23 months (95% CI: 16, 47) for IO/IO, p = 0.13. For TKI/IO and IO/IO groups, respective PFS-2 at 12 months was 86% (95% CI 77, 92) and 74% (95% CI 63, 82); PFS-2 at 36 months was 51% (95% CI 39, 63) and 42% (95% CI 30, 53). OS was not significantly different (p = 0.32; 3 year OS: IO/IO 60%, 95% CI 47, 71; TKI/IO 62%, 95% CI 49, 73). (Table) Conclusions: In patients receiving 1 st line IO/IO or TKI/IO, ORR 2nd was higher with IO/IO and median PFS-2 was numerically higher with TKI/IO, but no statistically significant difference in PFS-2 or OS was seen. These findings suggest that IO/IO and TKI/O are both acceptable 1 st line treatment strategies in ccRCC. [Table: see text]